• Population: Patients 18 years of age and older, presenting within six hours after the onset of ICH
  • Exclusions:
    • Definite evidence that the ICH is secondary to either a structural abnormality in the brain or previous thrombolysis
    • Attending clinician felt there was a high likelihood that the patient would not adhere to the study treatment and follow-up regimen
• Intervention: Bundled care per a goal-directed intensive care protocol to correct hypertension, hyperglycemia, pyrexia, and hypercoagulability, with the goal of achieving treatment targets within one hour of initiating treatment and maintaining them for seven days (or until discharge or death, whichever came first)
• Comparison: Usual care at the discretion of the treating physician
• Outcome:
  • Primary Outcome: Functional recovery measured at six months according to the modified Rankin Scale (mRS) score and analyzed as an ordinal outcome (shift across all categories)
  • Secondary Outcomes:
    • Functional recovery according to a shift analysis of scores on the National Institutes of Health Stroke Scale at seven days
    • Dichotomous mRS outcomes at six months (0-2 versus 3-6, and 0-2 versus 3-5)
    • Death at six months
    • Death or neurological deterioration at seven days
    • Health-related quality of life using the EuroQoL Group 5-Dimension self-report questionnaire
    • Residence at six months (own home versus other)
    • Time to hospital discharge
  • Safety Outcomes: All-cause and cause-specific serious adverse events, recorded for the duration of follow-up
• Type of Study: A pragmatic, international (10 countries), multicenter (121 hospitals), unmasked, stepped-wedge, cluster randomized, controlled trial

Authors’ Conclusions

“Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition.”

Results

A total of 7,036 patients were recruited from 121 hospitals that could be included in the modified intention-to-treat analysis. The mean age of patients was 62 years with 36 percent female. Most of the patients (over 90 percent) were Chinese.

Key Results

The odds of a poor functional outcome were lower in the care bundle group compared to usual care.

• Primary Outcome: mRS favored the care bundle group (OR, 0.86; 95 percent confidence interval, 0.76-0.97; P = 0.015), consistent across all adjustments and calculations.
• Secondary Outcomes: Most secondary outcomes did not show a statistically significant difference. Some showed trends in a positive direction. Patients who received the intervention were statistically more likely to be discharged by day seven. The EuroQoL Group 5-Dimension self-report questionnaire quality of life assessment was a mixed bag, but the effects on this scale diminished when they made the various statistical adjustments in their posthoc analysis.
• Safety Outcomes: There were significantly fewer serious adverse events in the bundled care group.

EBM Commentary

1. External Validity: It is unclear if this data applies to patient you see in your emergency department. One reason is where these patients were recruited to be included in the trial. The cohort came from nine low- and middle-income countries and one high-income country. Most of the patients were recruited from China (90 percent) with only 3 percent coming from Chile (the only one classified as a high-income country).